Hetero-Diels-Alder and Ring-opening Reactions of Furans Applied to the Synthesis of Functionalized Heterocycles

Furans were explored as scaffold for the synthesis of a range of heterocyclic compounds, exploring the dienophilic behaviour towards nitroso- and azoalkenes as the first step. Acid-catalysed rearrangements of these cycloadducts, 4a,7a-dihydro-4H-furo[2,3-e][1,2]oxazines and 1,4,4a,7a-tetrahydrofuro[3,2-c]pyridazines, were studied. Using 1 equivalent of TFA, the bicyclic heterocycles derived from furan and 2-methylfuran, are converted into furans bearing side-chains incorporating oxime and hydrazone groups by ring-opening of the six-membered ring with the concomitant aromatization of the furan ring. The use of TFA as solvent can lead to rearrangements via the generation of spirocyclic intermediates followed by furan ring-opening to afford functionalized isoxazoles or pyrazoles. Furthermore, furo-oxazines derived from 2,5-dimethylfuran, where furan aromatization is precluded, are converted efficiently into 6H-1,2-oxazines via a furan ring-opening reaction upon thermolysis in presence of a catalytic amount of p-toluenesulfonic acid. Tetrahydrofuro[3,2-c]pyridazines derived from furan and dimethylfuran undergo acid-catalyzed addition reaction, leading to 6-substitued-hexahydrofuro[3,2-c]pyridazines, when in presence of alcohols or water.